HENRY KAPLAN MEMORIAL LECTURE: “IMMUNOTHERAPY COMES OF AGE TO TREAT LYMPHOMAS”

Abstract

Introduction: Relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) is associated with a poor outcome once patients (pts) become resistant to traditional chemotherapy and new approaches are needed. Brentuximab vedotin (BV) is a novel anti-CD30 monoclonal antibody conjugated to the antimicrotubule cytotoxic monomethyl auristatin-E. BV has been licenced for use post autologous stem cell transplant (SCT) and in pts who have received 2 prior lines of therapy and unsuitable for SCT. Efficacy data are limited for BV as a 'bridge' to autologous or allogenic SCT. Methods: We performed a UK-wide retrospective multi-centre study of 99 SCT-naive R/R cHL to assess the success of incorporating BV pre-SCT. All had previously received >=2 prior chemotherapy lines with curative intent. Pts had all received prior salvage with the initial aim to proceed to potential curative SCT but were not deemed suitable due to failure to induce deep, durable remissions. (Figure Presented) Results: Patient characteristics are outlined in the Table. From the start of BV, the median progression-free survival (PFS) for all pts was 5.6 months (95% confidence interval (CI) 4.4 - 12.2 months) and median overall survival (OS) was 37.2 months (95% CI 18.3 months -not reached (NR)) (Figure A & B). The overall response by CT or PETCT to BV was 56% (complete metabolic response/complete response/complete response unconfirmed (CMR/CR/CRu) 29%; partial metabolic response/partial response (PMR/PR) 27%). 34% had a SCT after BV with no further treatment. 27% required further treatment post-BV pre-SCT.Pts consolidated with either an auto or alloSCT had a superior PFS (Figure C) and OS (Figure D) to those not receiving consolidative SCT (p < 0.001 for auto and alloSCT vs. non-SCT for median PFS (auto: NR (95% CI 17.0 months - NR) vs allo: NR (95% CI 5.6 months - NR) vs non-SCT: 3.0 months (95% CI 2.5 -4.4 months)). The median duration of response for pts entering CR was superior to PR, consistent with prior reports (Figure E). Using multivariate Cox regression, pts with improved performance status and haemoglobin at first relapse had improved PFS from the start of BV. Conclusion: We demonstrate that BV has effective activity (ORR 56%) allowing bridge to SCT in a cohort of high risk SCT-naive, predominantly refractory cHL. 34% are consolidated by SCT post-BV (median of 4 cycles) and a further 27% are salvaged to SCT following inadequate BV response. 39% do not reach SCT and have poor outcomes, with PFS of 3.0 months, demonstrating the unmet need to improve outcomes in those unsuitable for SCT.